Preparation, characterization, and physicochemical property of the inclusion complexes of Cannabisin A with ,B-cyclodextrin and hydroxypropyl- ,B-cyclodextrin

Cannabisin A (CA), derived from hemp seed shells, has antioxidant and anti-neuroinflammatory activity. However, its application is limited due to its poor solubility. In this work, ,B-cyclodextrin ( ,B-CD) and HP-,B-cyclodextrin (HP -,B-) were used to encapsulate CA to increase its water-solubility. The inclusion complexes of CA with ,B-CD (CA/,B-CD IC) and the inclusion complexes of CA with HP -,B-CD (CA/HP-,B- CD IC) were prepared by the aqueous ethanol solution method. The Job's plot assay and Phase solubility assay revealed that the inclusion complexes of CA with ,B-CD/HP-,B-CD formed at a 1:1 stoichiometric ratio. However, considering the inclusion process is reversible, the inclusion complexes were prepared at a 1:2 molar ratio. The structure of the inclusion complexes was identified by FT-IR, XRD, DSC, SEM, and NMR. In addition, the results of1 H NMR, 2D ROESY NMR, and molecular docking further determined the possible conformations of the inclusion complexes. The solubility of the CA in the CA/,B-CD IC and CA/HP-,B-CD IC was increased by 13.95-fold and 56.37-fold, respectively, compared to pure CA; and the dissolution and antioxidant activity of the CA were also significantly promoted after complexation. This study proved that CA/HP-,B-CD IC was the preferred inclusion complex compared to CA/,B-CD IC due to its better physicochemical properties. (c) 2022 Published by Elsevier B.V.